In recently completed studies it was found that the presence of high concentrations of leukemic cells (2 to 6 x 10 to the 4th power cells/mm3) in blood of leukemic rats perfused through isolated spleens of leukemic and nonleukemic rats depressed splenic clearance of colloidal gold. Reducing the concentration of leukemic cells less than 8 x 10 to the 3rd power cells/mm3) restored the clearance of codloidal gold to normal (control) values. There was no significant difference between the clearance of colloidal gold in spleens of leukemic and nonleukemic rats perfused with blood of nonleukemic rats on the basis of total spleen weight. However, clearance was significantly lower in the leukemic spleen on the basis of unit weight of splenic tissue. In contrast, the clearance of 99m Technetium-sulfur colloid in isolated spleens of leukemic rats perfused with blood of nonleukemic rats was significantly lower than in perfused of nonleukemic rats on the basis of both total spleen weight and unit weight of splenic tissue. The perfusion of blood of leukemic rats through nonleukemic spleens significantly depressed the clearance of 99mTc-s similar to the effect on colloidal gold. However, reducing the concentration of leukemic cells in the blood did not as for colloidal gold restore colloidal sulfur clearance to normal (control) values. These findings indicate that dissimilar colloids can be processed differently by the RES in this leukemia and demonstrates that to adequately assess RES function it is important to use more than one test agent. Current goals are to assess the effect of leukemic cells on RES function and to determine the stage in the development of leukemia in which RES function is altered.